This invention relates to an improved echo contrast agent for ultrasound echocardiography. More particularly, this invention relates to an improved echo contrast agent for use in ultrasonic echocardiography that can be introduced into the body through peripheral venous injection to opacify the left ventricle.
The use of echo contrast agent in ultrasound echo cardiography was introduced by Dr. Gramiak and his coworkers at the University of Rochester. Their initial work was published in an article entitled "Ultrasound cardiography: contrast studies in anatomy and function," Radiology, 92:929 (1969). When an ultrasonic beam strikes a surface or traverses a tissue interface, part of the energy is absorbed, part of the energy is reflected, and another part of the beam passes through the material. The returning pulses, caused by reflected waves, are displayed on an oscilloscope and recorded. In their studies, Dr. Gramiak et al. found that the intracardiac injection of indocyanine green dye produced a cloud of echoes on the echocardiogram. They attributed this contrast effect to the microbubbles that were suspended in the indocyanine green solution prior to injection. Since then indocyanine green dye has become standard contrast agent in ultrasound echocardiography.
Other contrast agents, such as saline, 5% dextrose in water, carbon dioxide gas, hydrogen peroxide, and even the patient's blood, have been used by many echocardiographers. Other contrast agents are discussed in a book entitled "Contrast Echocardiography" edited by R. S. Meltzer and J. Roelandt. Its content is incorporated by reference. In clinic studies, the contrast agent must be introduced via a cardiac catheter injection into the ascending aorta or the coronary arteries. Such a practice requires a highly skillful person to implement. It also suffers the risk of being injected into the body, and the need of a cardiac catheter placement. For clinic purposes, it is desirable to have an echo contrast agent that can be introduced into the body through peripheral venous injection. Such an echo contrast agent must also be able to traverse the pulmonary circulation and enhance the myocardial image during echocardiography.
In order to traverse the pulmonary circulation, the contrast agent must be able to generate microbubbles that are very small in volume and stable and will not partially or totally obstruct capillary blood flow. The microbubbles so generated must be able to traverse the pulmonary circulation without significant loss so that they can arrive at the left ventricle in substantial concentration to enhance the opacification thereof during echocardiography.
As mentioned hereinbefore, although there are quite a few echo contrast agents that are available for echocardiography, most of them cannot be introduced into the body via peripheral venous injection and are not capable of traversing the pulmonary circulation. Three echo contrast agents reported in the literature that can traverse the pulmonary circulation are described below:
(1) Albunex: This is an albumin-containing powder. Its exact composition has not been made public. It has been evaluated by researchers at several medical research centers; however, it is relatively expensive and is not yet commercially available. See J. of American College of Cardiology, Vol. 16, No. 2, 1990, pp. 316-324.
(2) SHU-508: This is a monosaccharide contrast agent, made by Schering Berlex Lab. The composition of this experimental agent has not been published. See J. of American College of Cardiology, Vol. 13, No. 7, 1989, pp. 1622-8.
(3) Gelifundal and intralipid solution: This agent has been used only at medical research center; it requires a dosage of at least 28 ml to be effective. See American Heart Journal, 1988, pp. 399-407.